Endothelin-1 (ET-1) has been shown to have a constrictor effect on the airways and parenchyma; however, the roles of the ETA and ETB receptors in the ET-1-induced changes in the airway and tissue compartments have not been fully explored. Low-frequency pulmonary impedance (ZL) was measured in anaesthetized, paralysed, open-chest guinea-pigs. ZL spectra were fitted by a model to estimate airway resistance (Raw) and inertance (Iaw), and coefficients of tissue damping (G) and elastance (H), and hysteresivity (η = G/H). Two successive doses of ET-1 (0.05 and 0.2 nmol·kg-1) each evoked significant dose-related increases in Raw, G, H, and η. Pretreatment with 20 nmol·kg-1 BQ-610 (a highly selective ETA receptor antagonist) resulted in a significantly decreased elevation only in H after the lower dose of ET-1. However, all parameters changed significantly less on the administration of ET-1 after pretreatment with 80 nmol·kg-1 BQ-610, with 20 nmol·kg-1 ETR-P1/fl (a novel ETA receptor antagonist) or with 20 nmol·kg-1 IRL 1038 (an ETB receptor antagonist). The results of the separate assessments of the airway and tissue mechanics demonstrate that endothelin-1 induces airway and parenchymal constriction via stimulation of both receptor types in both compartments.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine